Anti Amoebic Drugs

These drugs are not only effective against amoebia but also against some others:

Common diseases treated by these drugs

A)     Amoebiasis

In 10% of population (50 million people) causing around 100,000 deaths/year.

Causative organisms

1. Entamoeba histolytica –causes active disease
2. E. despar –cause 90% of infection but no symptoms occur, no treatment is required

These cannot be differentiated on light microscopy, but by PCR or ELISA.

Mode of transmission

• Feco-oral route via contaminated food, drinks, water, etc. man is the only host.
• Cysts of E. histolytica resist stomach acidity, they develop into trophozoites in gut, causing invasive disease.
• In distal GIT, trophozoites again convert into cysts, probably due to decreased water content. They are excreted in feces.
• Trophozoites cannot survive in the adverse conditions, but cysts are able to tolerate.

1.      Asymptomatic carriers

Can cause totally asymptomatic carrier state. They require treatment as are source of infection to others.

2.      Intestinal colitis

Mild to moderate –diarrhea like condition, stool with mucus or blood occasionally

Severe –flask shaped mucosal ulcers, which bleed, leading to dysentery

3. Perforation
4. Peritonitis
5. Appendicitis even
6. Hepatic abscess

In gut trophozoites enter circulation by reaching liver. They can cause amoebic liver abscess with high grade fever.

7.      Amoeboma

Appear like tumor, may form as constricting circulation ring in GIT.

8.      Other extraintestinal manifestations

e.g.

a. pneumonia

b. lung infection

c. brain abscess

Rampant in poor hygienic conditions, overcrowding, etc. even in hostels, mental hospitals.

B)    Giardiasis

Caused by

1. Giardia intestinalis
2. Giardia lamblia

May be asymptomatic.

May take the form of:

1. GIT irritation e.g. diarrhea (self limiting in 5 days)
2. Foul smelling stools
3. May be chronic:

i. Malabsorption due to steatorrhea

ii. Weight loss

C)     Trichomoniasis

An sexually transmitted disease, causing:

a. in males causing urethritis

b. in females causing vaginitis

If one partner is affected, others is treated as well, as it can be transmitted.

D)    Balantidiasis

• By B. coli
• Produces diarrhea similar to amoebiasis.

Chemical Classification

Nitroimidazole derivatives

• Metronidazole,
• Tinidazole, (fasigen)
• Secnidazole
• Benznidazole,
• Ornidazole,
• Nimorazole

Dichloroacetamide derivatives

• Diloxanide furoate (also used with metronidazole called entomazale)
• Clefamide,
• Teclozan,
• Etofamide

4- aminoquinoline derivatives

• Chloroquine

 

Alkaloids of Ipecacuanha

• Emetine, (very toxic)
• Dehydroemetine (less toxic)

Antibiotics

• Tetracycline
• Paromomycin
• Erythromycin

8-hydroxyquinoline derivatives

• Diiodohydroxyquin (iodoquinol) (comes with metronidazole called metodine)
• Clioquinol  (not used due to optic toxicity)

Misc.

• Nitazoxanide ( used against i. giardiasis ii. Amoebiasis)

Therapeutic classification

Drugs effective in luminal infection only

(some also have actions against cysts, so helpful in elimination of carrier state)

• Diloxanide furoate
• Diiodohydroxyquin
• Tetracyclines,
• Paromomycin

Drugs effective in hepatic and tissue amoebiasis only

• Chloroquine,
• Emetine,
• Dehydroemetine

Drugs effective in luminal & tissue amoebiasis (though less in lumen)

Not effective against cysts

• Metronidazole,
• Tinidazole,
• Secnidazole,
• Ornidazole

Usually combined with luminal agents.

Tinidazole, Secnidazole and Ornidazole

Mechanism of Action

Similar to metronidazole. Can be used in single dose instead of 7-10 days.

Therapeutic uses

Tinidazole –against microaerophilic bacteria

Usually against anaerobic bacteria but not bacteriodes species.

Emetine and Dehydroemetine

Source

Natural, obtained from Ipecac root (Brazil root), used in older days for inducing vomiting when gastric lavage was not available.

Acts by:

1. direct irritation
2. effects CTZ

Dehydroemetine is synthetic and has less toxic profile than emetine.

Pharmacokinetics

Always parentally (I/M or S/C but never I/V or orally).

Cumulative action especially deposit in liver, kidneys, spleen and lungs.

Half life is 5 days.

Excretion is by urine –even after 1-2 months of therapy it is excreted.

Mechanism of Action

Inhibit protein synthesis as prevent movement of ribosomes on mRNA.

Also effective against E. histolytica.

Have:

1. alpha blocking property
2. anti-cholinergic property

Indications

1. Tissue amoebiasis –when metronidazole not available or C/I
2. Ballentidiasis

Adverse effects

Local:

1. pain at site of injection
2. sterile abscess may form
3. weakness of muscles when injected

GIT

1. stimulate CTZ
2. nausea
3. vomiting
4. diarrhea
5. abdominal discomfort

CVS

1. severe hypotension (alpha blocking activity)
2. reflex tachycardia
3. arrhythmias (atrial, ventricular)
4. precipitation of CCF
5. ECG abnormalities, e.g.
   1. T wave flattening or inversion
   2. Prolongation of QT interval

So should be used only when:

1. patient is hospitalized
2. being monitored

Misc

1. dizziness
2. headache
3. rash

toxicity is decreased when used for 3-5 days. It occurs when used for more than five days.

Contraindications

1. children
2. renal disease
3. cardiac problems
4. pregnancy

Chloroquine (Anti-amoebic use mentioned only)

Reserved for hepatic amoebic abscess disease because it gets concentrated in liver. May be more than 100 times than in plasma. It has special affinity for hepatocytes.

Mechanism of Action

Direct amoebicidal to E. histolytica

Well absorbed from GIT, very little reaches colon. So less effects on GIT amoeba. Thus used with luminal agents.

Dose

1 g for 2 days.

Then 500 mg for 2- 3 days.

Adverse Drug Reactions

1. nausea
2. vomiting
3. dizziness
4. no danger of retinopathy or neuropathy (only occurs when used for long time in rheumatoid arthritis)

Diloxanide Furuate

Mechanism of Action

In intestine splits to

1. diloxanide
2. furaic acid

Diloxanide is 90% absorbed,

10% is unabsorbed-which is therapeutically active.

Exact mechanism is not known.

Adverse Drug Reactions

1. flatulence –common
2. abdominal discomfort
3. skin rashes

Used alone only I/M for asymptomatic carriers.

Otherwise combined with metronidazole.

Iodoquinol

Has iodine in structure.

Usually well tolerated if not used for more than 20 days.

Mechanism of Action

Luminal agent.

Exact mechanism is not known.

Dose

650 mg thice daily.

Also used in combination with metronidazole called metodine.

Adverse Drug Reactions

1. Neuropathy
2. Optic neuritis in children
3. GIT
   • nausea
   • vomiting
   • diarrhea

   4. Signs of iodine toxicity e.g.

   • pruritis
   • urticaria
   • fever

Paromomycin

An aminoglycoside.

Luminal agent

Also acts indirectly.

Mechanism of Action
binds 30S subunit, resulting in misreading and inhibition of formation of initiation complex.

Pharmacokinetics

No absorbed orally.

Destroys bacteria on which amoeba feeds, so indirect killing.

Not used I/V, otherwise toxicity occurs, as with other aminoglycosides.

Therapeutic uses

1. amoebiasis
2. Giardiasis
3. Cutaneous leishmaniasis –topically

Tetracyclines

Mechanism of Action

Same as previously described.

Destroy bacteria on which amoeba feed.

Indirect killing like aminoglycosides.

Contraindications

Not used in children less than 8 years of age.

Can be combined with metronidazole.

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Metronidazole